Is RBFOX3 p.Pro323= (c.969C>T) pathogenic?

RBFOX3 p.Pro323= (c.969C>T) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-15). Rare (popmax 0.274%, eas); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro323= (c.969C>T)?

RBFOX3 p.Pro323= (c.969C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro323= (c.969C>T) in the general population?

RBFOX3 p.Pro323= (c.969C>T) is rare (popmax 0.274%, eas) (gnomAD).

RBFOX3 p.Pro323=

c.969C>T · rs570994105 · VCV697807

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.274%, eas)

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14	GERP -3.8
Overall
CADD	0.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.274% East Asian · 112/40,904 alleles

Filtering AF 0.233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.217%

Overall 0.0102% 159/1,551,416 alleles · rare exomes 133/1,399,076 · genomes 26/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.274%	365
African / African-American	0.0328%	3,049
Admixed American	0.0177%	5,666
Remaining individualsnot grpmax-eligible	0.00832%	12,022
South Asian	0.00119%	84,008
European (non-Finnish)	0.000698%	143,350

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RBFOX3
Protein: p.Pro323=
Coding: c.969C>T
MANE Select: NM_001350451
dbSNP: rs570994105
Type: single nucleotide variant
Location: chr17:79095542 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27

Full RBFOX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

idiopathic generalized epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBFOX3 p.Ala316Thr Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala62Val Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala68Thr Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala79Val Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala8Thr Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Arg230Trp Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Gln31Arg Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Glu61Lys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rbfox3-p-pro323 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown